Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT).

BACKGROUND: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19. OBJECTIVE: Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19. METHODS: This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand. RESULTS: As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024. CONCLUSIONS: This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48183.

Age Moderates the Effect of Obesity on Mortality Risk in Critically Ill Patients With COVID-19: A Nationwide Observational Cohort Study.

OBJECTIVES: A high body mass index (BMI) is associated with an unfavorable disease course in COVID-19, but not among those who require admission to the ICU. This has not been examined across different age groups. We examined whether age modifies the association between BMI and mortality among critically ill COVID-19 patients. DESIGN: An observational cohort study. SETTING: A nationwide registry analysis of critically ill patients with COVID-19 registered in the National Intensive Care Evaluation registry. PATIENTS: We included 15,701 critically ill patients with COVID-19 (10,768 males [68.6%] with median [interquartile range] age 64 yr [55-71 yr]), of whom 1,402 (8.9%) patients were less than 45 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the total sample and after adjustment for age, gender, Acute Physiology and Chronic Health Evaluation IV, mechanical ventilation, and use of vasoactive drugs, we found that a BMI greater than or equal to 30 kg/m 2 does not affect hospital mortality (adjusted odds ratio [OR adj ] = 0.98; 95% CI, 0.90-1.06; p = 0.62). For patients less than 45 years old, but not for those greater than or equal to 45 years old, a BMI greater than or equal to 30 kg/m 2 was associated with a lower hospital mortality (OR adj = 0.59; 95% CI, 0.36-0.96; p = 0.03). CONCLUSIONS: A higher BMI may be favorably associated with a lower mortality among those less than 45 years old. This is in line with the so-called "obesity paradox" that was established for other groups of critically ill patients in broad age ranges. Further research is needed to understand this favorable association in young critically ill patients with COVID-19.

Electrical Impedance Tomography As a Bedside Diagnostic Tool for Pulmonary Embolism.

Electrical impedance tomography (EIT) has been shown to be of value in evaluating the distribution of ventilation. In addition, several studies, particularly case reports, have demonstrated the use of EIT in the assessment of lung perfusion. EIT may be a potential diagnostic bedside tool in the diagnosis and follow-up of acute pulmonary embolism. CASE SUMMARY: We present one case of a patient with COVID-19 who likely had pulmonary thromboembolism where perfusion scans were made before and after thrombolytic therapy. Perfusion scans showed improvement after thrombolytic therapy. This article should therefore be seen as a first step in proving the validity of EIT-derived perfusion scans as a diagnostic for pulmonary embolism. CONCLUSION: The hypertonic saline bolus EIT method as a diagnostic tool for pulmonary embolism is a promising new technique, which can be particularly meaningful for critically ill patients. Further study is required to evaluate the sensitivity and specificity of this technique and the impact on decision-making and outcomes of critically ill patients.

Increased mortality in ICU patients ≥70 years old with COVID-19 compared to patients with other pneumonias.

BACKGROUND: Patients over 70 years old represent a substantial proportion of the COVID-19 ICU population and their mortality rates are high. The aim of this study is to describe the outcomes of patients ≥70 years old admitted to Dutch ICUs with COVID-19, compared to patients ≥70 years old admitted to the ICU for bacterial and other viral pneumonias, with adjustments for age, comorbidities, severity of illness, and ICU occupancy rate. METHODS: Retrospective cohort study including patients ≥70 years old admitted to Dutch ICUs, comparing patients admitted with COVID-19 from March 1st 2020 to January 1st 2022 with patients ≥70 years old admitted because of a bacterial and other viral pneumonia, both divided in a historical (i.e., January 1st 2017 to January 1st 2020) and current cohort (i.e., March 1st 2020 to January 1st 2022). Primary outcome is hospital mortality. RESULTS: 11,525 unique patients ≥70 years old admitted to Dutch ICUs were included; 5094 with COVID-19, 5334 with a bacterial pneumonia, and 1312 with another viral pneumonia. ICU-mortality and in-hospital mortality rates of the patients ≥70 years old admitted with COVID-19 were 39.7% and 47.6% respectively. ICU- and hospital mortality rates of the patients who were admitted in the same or in an historical time period with a bacterial pneumonia or other viral pneumonias were considerably lower (19.5% and 28.6% for patients with a bacterial pneumonia in the historical cohort and 19.1% and 28.8% in the same period, for the patients with other viral pneumonias 20.7% and 28.9%, and 22.7% and 31.8% respectively, all p < 0.001). Differences persisted after correction for several clinical characteristics and ICU occupancy rate. CONCLUSIONS: In ICU-patients ≥70 years old, COVID-19 is more severe compared to bacterial or viral pneumonia.

Electrical Impedance Tomography As a Bedside Diagnostic Tool for Pulmonary Embolism

BACKGROUND: Electrical impedance tomography (EIT) has been shown to be of value in evaluating the distribution of ventilation. In addition, several studies, particularly case reports, have demonstrated the use of EIT in the assessment of lung perfusion. EIT may be a potential diagnostic bedside tool in the diagnosis and follow-up of acute pulmonary embolism. CASE SUMMARY: We present one case of a patient with COVID-19 who likely had pulmonary thromboembolism where perfusion scans were made before and after thrombolytic therapy. Perfusion scans showed improvement after thrombolytic therapy. This article should therefore be seen as a first step in proving the validity of EIT-derived perfusion scans as a diagnostic for pulmonary embolism. CONCLUSION: The hypertonic saline bolus EIT method as a diagnostic tool for pulmonary embolism is a promising new technique, which can be particularly meaningful for critically ill patients. Further study is required to evaluate the sensitivity and specificity of this technique and the impact on decision-making and outcomes of critically ill patients.

Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. METHODS: This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. DISCUSSION: Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662 European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL.

Developing and testing a nurse-led intervention to support bereavement in relatives in the intensive care (BRIC study): a protocol of a pre-post intervention study.

BACKGROUND: When a patient is approaching death in the intensive care unit (ICU), patients' relatives must make a rapid transition from focusing on their beloved one's recovery to preparation for their unavoidable death. Bereaved relatives may develop complicated grief as a consequence of this burdensome situation; however, little is known about appropriate options in quality care supporting bereaved relatives and the prevalence and predictors of complicated grief in bereaved relatives of deceased ICU patients in the Netherlands. The aim of this study is to develop and implement a multicomponent bereavement support intervention for relatives of deceased ICU patients and to evaluate the effectiveness of this intervention on complicated grief, anxiety, depression and posttraumatic stress in bereaved relatives. METHODS: The study will use a cross-sectional pre-post design in a 38-bed ICU in a university hospital in the Netherlands. Cohort 1 includes all reported first and second contact persons of patients who died in the ICU in 2018, which will serve as a pre-intervention baseline measurement. Based on existing policies, facilities and evidence-based practices, a nurse-led intervention will be developed and implemented during the study period. This intervention is expected to use 1) communication strategies, 2) materials to make a keepsake, and 3) a nurse-led follow-up service. Cohort 2, including all bereaved relatives in the ICU from October 2019 until March 2020, will serve as a post-intervention follow-up measurement. Both cohorts will be performed in study samples of 200 relatives per group, all participants will be invited to complete questionnaires measuring complicated grief, anxiety, depression and posttraumatic stress. Differences between the baseline and follow-up measurements will be calculated and adjusted using regression analyses. Exploratory subgroup analyses (e.g., gender, ethnicity, risk profiles, relationship with patient, length of stay) and exploratory dose response analyses will be conducted. DISCUSSION: The newly developed intervention has the potential to improve the bereavement process of the relatives of deceased ICU patients. Therefore, symptoms of grief and mental health problems such as depression, anxiety and posttraumatic stress, might decrease. TRIAL REGISTRATION: Netherlands Trial Register Registered on 27/07/2019 as NL 7875, www.trialregister.nl.